The present invention is generally related to probing surfaces by spectroscopic and imaging techniques, where the signal being measured is generated by a hyperpolarized gas having a nuclear electric quadrupole moment.
Sensitive, reliable and robust techniques that provide information about a surface are important for a variety of industries. For example, surface probing can provide further understanding of surface chemistry, geometry and physical properties. Such understanding is important in diverse and wide-ranging applications, including materials science, manufacturing and surface patterning processes (ranging from the nano- and micro-size to large scale), drug delivery, and catalysis studies, to name but a few. It can be difficult to obtain useful, reliable and sensitive surface information by surface probing using conventional techniques. In particular, techniques known in the art are generally most useful for a relatively narrow range of situations. For example, optical-based techniques are generally ill-suited for porous surfaces and/or surfaces that are not visually accessible (e.g., located within an opaque medium). Other techniques, such as nuclear magnetic resonance (NMR) spectroscopy or magnetic resonance imaging (MRI) provide an ability to image optically inaccessible surfaces, but often suffer from limitations associated with the compound that is generating a detectable signal such as low signal intensity due to the low number of surface molecules and the inability to distinguish between signal arising from the surface and signal arising from the bulk material.
For example, a promising technique known in the art relies on hyperpolarized (hp) 3Helium (He) and hp 129Xenon (Xe), both having nuclear spin I=½, for use in a number NMR and MRI applications. The high spin polarization obtained through rubidium vapor spin exchange optical pumping (RbSEOP) leads to signal enhancements of many orders of magnitude over that obtained from thermal polarization and allows for applications that are otherwise not feasible.
One surface that is generally optically inaccessible, is an in vivo lung. A variety of MRI techniques have been used to image the lung, including lungs from a healthy subject and from a smoker, wherein multiple ventilation defects are observed. One such technique is hp 3He MRI. For examples of such images, see Edwin et al. The Proceedings of the American Thoracic Society 2:528-532 (2005) Hyperpolarized 3-Helium Magnetic Resonance Imaging to Probe Lung Function; Brookeman et al. (1998) Polarized Gas Targets and Polarized Beams: Seventh International Workshop, edited by Roy J. Holt and Michael A. Miller (1998) The American Institute of Physics. Polarized Noble Gas MRI; Jurasek (2003) Dynamic MRI Enables Airway Visualization 8(9). One of the fundamental parameters with high diagnostic value for hp 3He MRI is the spin density that is a result of the helium concentration in a particular volume. Spin density mapping of hp 3He can be applied to visualize ventilation in lungs. For example, a two dimensional fast low angle shot (FLASH) hp 3He magnetic resonance image of the lungs of a healthy subject is obtained in a single breath hold after inhalation of about one liter of hp 3He gas. The image shows a uniform distribution of the hp 3He gas which displays high signal intensity as brighter areas of the magnetic resonance image. Images obtained from the lung of a middle-aged heavy smoker which shows multiple ventilation defects in both lungs. See for example, deLange, Edward et al., “Lung Air Spaces: MR Imaging Evaluation With Hyperpolarized 3He Gas”, Radiology 210: (3) 851-857 (1999), hereby incorporated by reference. That technique, however, does not provide adequate surface contrast, and suffers from an inability to analyze surface chemistry in detail.
In vivo MRI of airways with hp 129Xe as a contrast agent suffers from a lower sensitivity compared to hp 3He. However, 129Xe adds a further parameter not available by 3He, namely the chemical shift that allows for insights into the local environment of the xenon atoms. The 129Xe chemical shift has been used extensively for research in materials science, engineering and for xenon dissolved in liquids including human blood. The chemical shift obtained from hp 129Xe can be used to generate an in vivo MRI contrast that is a probe for exchange of the gaseous xenon with the lung parenchyma. See, Ruppert et al., ‘Probing lung physiology with xenon polarization transfer contrast (XTC)’, MAGNETIC RESONANCE IN MEDICINE 44 (3): 349-357 SEPTEMBER 2000; and Driehuys et al., ‘Imaging alveolar-capillary gas transfer using hyperpolarized Xe-129 MRI’, PNAS 103 (48): 18278-18283 Nov. 28, 2006 44 (3): 349-357 SEPTEMBER 2000, hereby incorporated by reference).
3He and 129Xe are the only spin I=½ stable isotopes of the noble gas group, but there are three more NMR active isotopes in this group with higher nuclear spin (I>½) that possess a nuclear electric quadrupole moment. The three quadrupolar isotopes are 21Neon (Ne) (I= 3/2, natural abundance 0.27%), 83Krypton (Kr) (I= 9/2, natural abundance 11.5%) and 131Xe (I= 3/2, natural abundance 21%). Importantly, these noble gases have quadrupolar interactions capable of causing spin relaxation and coherent spin evolution. The methods disclosed herein rely on these quadrupolar interactions to probe surfaces, thereby characterizing the shape, size and symmetry of void spaces in porous media, for example. Furthermore, such probing by detecting quadrupolar interactions are useful in characterizing the chemical composition of surfaces. Therefore, the information provided by hp 21Ne, hp 83Kr, and hp 131Xe is itself useful, and particularly can be incorporated into conventional hp-noble gas imaging systems to provide information that is highly complementary to that obtained from those hp 3He and hp 129Xe systems. See for example, FIG. 1, which shows thermally polarized liquid 131Xe used to generate a T2 relaxation weighted MRI contrast in aerogels dependent on the adsorption of water onto the surface (as discussed by Meersmann, T. et al., “Probing Aerogels By Multiple Quantum Filtered 131Xe NMR Spectroscopy”, J. Am. Chem. Soc., 123, 941-945 (2001), hereby specifically incorporated by reference).
Unfortunately there are substantial impediments related to the use of hp 21Ne, hp 83Kr, and/or hp 131Xe in a surface-probe technique. A first problem with using 21 Ne, 83Kr, or 131Xe is that low thermal signal intensities make conventional gas phase MRI of these additional quadrupolar noble gases impractical. Moreover, high spin polarization of hp 21Ne, hp 83Kr, hp 131Xe by RbSEOP in previous work results in the presence of alkali metals, thereby prohibiting the use of these noble gases for MRI and NMR spectroscopy of reactive surfaces. Although alkali metal vapor spin exchange optical pumping of noble gas isotopes with quadrupolar nuclei has been explored previously, those studies suffer from the limitation that the paramagnetic and highly reactive alkali metal vapor (e.g., Rb) used in optical pumping (e.g., RbSEOP) is not removed. The removal of the reactive alkali metal from the hp-gas has not been previously attempted because of the additional time such removal process requires. It is unclear whether the generated high spin polarization would survive this removal process. Furthermore, it is unclear that an alkali metal vapor free I>½ noble gas is even useful for the study of, for example, porous media since the relaxation times in porous media are typically much shorter than the relaxation times in the gas phase. Therefore, it is unclear whether the spin polarization is capable of surviving transport into the porous media or sample area.
It is necessary to separate the alkali metal vapor for medical and most materials applications. The major obstacle for the production of Rb-free (or free of other alkali metals that may be used for the pumping process) hp 21Ne, hp 83Kr, or hp 131Xe can be attributed to the nuclear electric quadrupole moment, which significantly shortens the longitudinal relaxation (T1) times. The problem is illustrated by the longitudinal relaxation times of the two NMR active isotopes of the noble gas xenon. 129Xe (I=½) has a gas-phase T1 time on the order of 2 hours (h) at near ambient pressures and temperatures, but a T1 relaxation time of only 25 seconds (s) has been reported for pure gas phase 131Xe (I= 3/2) at 100 kilopascal (kPa). This relaxation time is further reduced to a T1 of typically only a few seconds for 131Xe in 8-12 mm diameter glass containers at the same pressure, ambient temperature, and 9.4 Tesla (T) field strength. Relaxation times of only a few seconds are too short in duration in the context of conventional RbSEOP, alkali metal vapor removal, and transfer of the hp gas to a detection cell to be of practical use in NMR and MRI applications.
While the quadrupole moment of 83Kr (0.26×10−28 m2) is about twice that of 131Xe (0.12×10−28 m2), the quadrupole interactions can be smaller for krypton compared to xenon due to krypton's larger nuclear spin, smaller and less polarizable electron cloud, and smaller Sternheimer antishielding factor. The reduced quadrupolar interactions for krypton are reflected in a longer T1 of 470 s that is expected in the absence of container walls at 300 Kelvin (K), 100 kPa, and 2.1 T (18). Even in 10 to 12.5 mm diameter and 4-5 cm long glass cylinders, the T1 times can be 90-150 s at 297 K, 100-200 kPa, and 9.4 T, depending on the glass surface treatment. However, significant signal loss due to krypton container wall interactions currently constrain signal enhancement well below the theoretical limit.
Noble gases with spin I>½ have an additional parameter that is not available with spin=½ noble gas isotopes: the nuclear electric quadrupole moment. The nuclear electric quadrupole moment may provide information about surfaces, but also causes rapid loss of the hyperpolarization (i.e., depolarization). Like in the case of spin=½ noble gas isotopes, alkali metal vapor spin exchange optical pumping may provide increased signal intensity for spin >½ noble gas isotopes. However, the inherently fast self relaxation of these noble gas isotopes lead to the conclusion that the removal of the reactive alkali metal vapor is either not feasible or not worthwhile. Fast self relaxation of these I>½ noble gas isotopes during the purification process or during insertion into a sample area containing surfaces, was considered to be a powerful depolarization process that would leave little signal intensity for NMR detection. The resulting remaining NMR signal was considered to be mediocre at best and not worth the effort. We demonstrate that a strong hyperpolarization in purified (ie. purified from alkali metal vapor) spin I>½ noble gasses is indeed feasible. Building on this success, we use hyperpolarized spin I>½ noble gas isotopes to probe surfaces. The methods disclosed herein are based on probing surfaces with hyperpolarized and purified I>½ noble gas isotopes using quadrupolar interactions during surface contact that allow information to be extracted about the surfaces.
Although there has been interest in spin I=½ hp-noble gasses in material sciences, and in MRI as diagnostic probes for pulmonary diseases (Raftery et al. Phys. Rev. Lett. 66: 584-7 (1991); Goodson J. Magn Reson. 155:157-216 (2002); Moller et al. Mag. Res. Med. 47:1029-51 (2002); U.S. Pat. Nos. 6,818,202, 6,666,047, 6,593,144), those studies suffer from a variety of limitations including the gas being insensitive or incompatible with obtaining information about surface chemistry. Although this sensitivity can be obtained by using I>½ noble gas isotopes, the lack of signal intensity makes the usage of thermally polarized noble gasses unpractical. Previous work reports use of hyperpolarized I>½ noble gasses (Butscher et al., Chem. Phys. Lett., 249 (1996) 444-450; Butscher et al., J. Chem. Phys., 100 (1994) 6923-6933), but the lack of separation from the reactive alkali metal vapor prohibits their use for probing reactive surfaces. In particular, reactive surfaces of interest for surface probing such as lung parenchyma, hydrated surfaces, surfaces having reactive deposits (e.g., from tobacco smoke), react with alkali metal vapor such as rubidium. Prior to the work reported herein, it was unclear whether alkali metal vapor-free hyperpolarized I>½ noble gas isotopes would be effective for imaging reactive surfaces that induce signal loss and whether they could be used for surfaces that may require a time length for exposure to the hyperpolarized gas that is on the order of the time that the hyperpolarized gas relaxes to its non-hyperpolarized state. Indeed, some nano-porous media such as zeolites may exhibit relaxation times that prohibit the usage of hyperpolarized I>½ noble gas isotopes for their study. Furthermore, many of the hp-gasses previously used (e.g., 3He and xenon gas) are, unlike krypton, difficult and expensive to obtain (e.g., 3He is obtained exclusively through tritium decay from weapons-related programs) or have anesthetic properties in the case of xenon that may cause problems for use in human medical imaging, making its use as biological imaging tool problematic.
From the foregoing, it is apparent that there is a need in the art for a hp-noble gas that provides the capability to measure a number of useful surface properties by NMR and/or MRI that is sensitive and selective, while ensuring the noble gas is generated in a cost-effective manner without having an adverse biological impact and without altering surfaces that are of interest for materials science and related applications. It is further apparent that there is a need for methods that improve information generated from NMR spectroscopy and MRI, so that more accurate and detailed analysis of surfaces, and particularly reactive surfaces, under study is obtained. As will be apparent, the present invention addresses this need by employing a noble gas whose properties are very sensitive to surface interactions.
The herein disclosed methods are based on the availability of hyperpolarized and purified (i.e. alkali metal vapor free) noble gas isotopes with spin I>½. The inventors demonstrate that alkali metal vapor spin exchange optical pumping followed by a separation process is one means for providing hyperpolarized and purified gasses. In addition, a number of alternative techniques may emerge in the future that may permit production of noble gases having spin I>½ without using alkali metal vapor, therefore making the purification process unnecessary. An example of an alternative polarization technique that produces a hyperpolarized state without alkali metal vapor is metastability-exchange pumping for hyperpolarizing 3He (Suchanek et al. “Hyperpolarized He-3 gas production by metastability exchange optical pumping for magnetic resonance imaging” OPTICA APPLICATA 35 (2): 263-276 2005; Kauczor et al. “MRI using hyperpolarized noble gases”, EUROPEAN RADIOLOGY 8 (5): 820-827 1998). Most likely, that technique may become useful for the hyperpolarization of 21Ne (INARD M, LEDUC M, “STUDY OF METASTABILITY EXCHANGE IN NEON BY OPTICAL-PUMPING”, JOURNAL DE PHYSIQUE 38 (6): 609-622 1977), but the production of hp 83Kr and hp-131Xe may also follow. Another example of an alternative polarization technique is dynamic nuclear polarization (DNP), a method that recently has been used to produce hyperpolarized molecules (Ardenkjaer-Larsen et al. “Increase in signal-to-noise ratio of >10,000 times in liquid-state NMR” PNAS 100 (18): 10158-10163 Sep. 2, 2003). Another alternative polarization technique that is known to produce hyperpolarized noble gasses with the nuclear spin I=½ is the ‘brute force technique’ (Krjukov EV, O'Neill J D, Owers-Bradley JR, ‘Brute force polarization of Xe-129’, JOURNAL OF LOW TEMPERATURE PHYSICS 140, 397-408, 2005; Biskup N, Kalechofsky N, Candela D, ‘Spin polarization of xenon films at low-temperature induced by He-3’, PHYSICA B-CONDENSED MATTER 329, 437-438, 2003). In brute force polarization, a very high polarization at thermal equilibrium at very low temperatures is utilized followed by a rapid warming of the sample. None of those hyperpolarization techniques, however, have been used to date to produce hyperpolarized noble gases having a nuclear electric quadrupole moment that are used in NMR and/or MRI methods for probing a surface.